The proposed research is designed to 1) identify and map Ia loci controlling cell surface determinants which are selectively expressed in immunocompetent cell subsets, 2) determine the immunobiological role of and interactions among subsets bearing distinct Ia products, 3) explore the role these products play in the generation or suppression of immunity, and 4) determine how epistasis (gene-gene interaction) influences the cell surface expression of Ia determinants. Restricted antisera will be prepared against products of distinct Ia loci. Tests for expression of these loci in different immunocompetent cell subsets will be conducted in negative selection experiments utilizing antiserum plus complement. We will also attempt to positively select for Ia-bearing subsets. Expression of Ia loci in suppressor T, helper T, and macrophage subsets will be determine in Mishell-Dutton in vitro antibody cultures. In particular, we will focus study on two new I-J bearing T cell subsets which inhibit suppressor activity by blocking (inactivating?) suppressor T cells and/or augmenting (amplifying?) helper activity. Utilizing selectively expressed Ia markers, and T cell-derived soluble mediators (factors), we will determine how distinct subsets interact with and regulate one another, and the role Ia loci play in this process. The ultimate goal of this study is to establish a firm base for elucidating the precise immunobiological role of Ia loci and the cells in which they are expressed.